On the involvement of calpains in the degradation of the tumor suppressor protein p53

FEBS Letters

Ciechanover, Aaron¹  Kosower, Nechama S.²  Barnoy, Sivia²  Shkedy, Dganit¹  Gonen, Hedva¹ 

[1] Department of Biochemistry and the Rappaport family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa 31096, Israel;Department of Human Genetics, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel

关键词: Calpain;    p53;    Ubiquitin;    Proteolysis;    ALLM;    N-acetyl-Leu-Leu-methioninal;    ALLN;    N-acetyl-Leu-Leu-norleucinal;    CM;    carboxymethyl;    DEAE;    diethylaminoethyl;    E1;    ubiquitin-activating enzyme;    E2 or UBC;    ubiquitin-carrier protein or ubiquitin-conjugating enzyme;    E3;    ubiquitin-protein ligase;    HPV;    human papillomavirus;    MG115;    carbobenzoxyl-Leu-Leu-norvalinal;    STI;    soybean trypsin inhibitor;   

DOI  :  10.1016/S0014-5793(97)00225-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A crude fraction that contains ubiquitin–protein ligases contains also a proteolytic activity of ∼100 kDa that cleaves p53 to several fragments. The protease does not require ATP and is inhibited in the crude extract by an endogenous ∼250 kDa inhibitor. The proteinase can be inhibited by chelating the Ca²⁺ ions, by specific cysteine proteinase inhibitors and by peptide aldehyde derivatives that inhibit calpains. Purified calpain demonstrates an identical activity that can be inhibited by calpastatin, the specific protein inhibitor of the enzyme. Thus, it appears that the activity we have identified in the extract is catalyzed by calpain. The calpain in the extract degrades also N-myc, c-Fos and c-Jun, but not lysozyme. In crude extract, the calpain activity can be demonstrated only when the molar ratio of the calpain exceeds that of its native inhibitor. Recent experimental evidence implicates both the ubiquitin proteasome pathway and calpain in the degradation of the tumor suppressor, and it was proposed that the two pathways may play a role in targeting the protein under various conditions. The potential role of the two systems in this important metabolic process is discussed.

【 授权许可】

Unknown